Evaluation of the cardiovascular toxic effect of recombinant interleukin-2 in rats.
Cardiac and vascular toxicity of recombinant interleukin-2 (rIL-2) was evaluated by in vitro and in vivo experiments in rats. Using isolated spontaneously beating atria, no changes were detected in heart rate or myocardial contractility in response to rIL-2 treatment at concentrations ranging from 0.1-100 U/ml. Daily sc administration of rIL-2 for 7 consecutive days (at doses of 2.3 X 10(4) to 1.15 X 10(6) U/ml) produced a prolongation of the QaT interval and significant modifications in serum electrolyte concentrations. Ex vivo contractility of atria excised at the end of rIL-2 treatment showed no deterioration in myocardial contractility with increasing dosage. rIL-2, at concentrations of 0.1-1000 U/ml, did not induce any modification of perfusion pressure in isolated rat tail artery but produced a significant displacement to the left of the dose-response curves for norepinephrine compared to basal conditions. The relative potencies were not dose-dependent. Our results indicate that rIL-2 does not exert a direct cardiotoxic effect, and suggest an indirect action on vascular smooth muscle, i.e., an aspecific modulation of vascular response to mediators.
Favalli
L
L
Cattedra di Saggi e Dosaggi Farmacologici, Università di Pavia, Italy.
Lanza
E
E
Rozza
A
A
Galimberti
M
M
Villani
F
F
D000818:Animals; D016275:Atrial Function; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D007376:Interleukin-2 / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000633:toxicity
D004573:Electrolytes; D007376:Interleukin-2; D011994:Recombinant Proteins; D009638:Norepinephrine